By: 17 March 2014
Ovarian cancer biomarker

A research team has found that the biomarker miR-181a is a molecular driver of epithelial ovarian cancer (EOC), which may help predict patients’ responses to treatment.

“By looking at the expression of this microRNA in tumour samples, we get an idea which women may respond to standard chemotherapy and which are at a high risk for recurrence,” said Analisa DiFeo, an assistant professor of General Medical Science-Oncology at the Case Comprehensive Cancer Center, and research team leader. “This helps guide treatment decisions and improve survival rates.”

In the past, researchers have been unable to predict how EOC patients will respond to treatment. This marks the first time scientists have demonstrated that a single miRNA increases the cellular survival, drug resistance and tumour metastasis of ovarian cancer cells by activating TGF-β, a potent cancer-signalling pathway.

“Prognostic markers and early detection markers for ovarian cancer have been elusive,” says Stanton Gerson, MD, Professor of Haematological Oncology, Director of the Case Comprehensive Cancer Center and Director of the Seidman Cancer Center at UH Case Medical Center. “This study is one of the first to indicate that it is possible using a novel genomic analysis to identify abnormalities specific to ovarian cancer. Women worldwide will benefit from this discovery.”

Ninety percent of all women with ovarian cancer have the EOC subtype, which is the fifth-leading cause of cancer deaths in women worldwide, with 15,000 deaths and 23,000 new cases each year. Because EOC is generally asymptomatic, most women are at an advanced stage (Stage 3-4) by the time they are diagnosed. Approximately 70-80 percent of patients who survive the disease after the first onset go on to face a recurrence.

DiFeo’s findings, published in Nature Communications, provide new insights into the role of miRNAs as treatment biomarkers. MicroRNA like miR-181a fine-tune the expression of as much as 60 percent of all protein-encoding genes.

DiFeo’s team screened the expression of miRNAs in both primary and recurrent human ovarian tumours, finding that miR-181a one of the most expressed miRNAs in tumours of people who had recurred in the first six months after treatment, and that it was in higher levels in recurrent tumours than primary. Her team discovered that this biomarker blocks the expression of the Smad7 gene, which generally shuts down the TGF-β signalling pathway, a potent inducer of metastases.

“We’re now looking for small molecules that can block the interaction between miR-181a and Smad7, stop TGF-β activation and prevent this micro-RNA from spreading and disseminating ovarian cancer,” DiFeo said. Until this discovery is made, DiFeo suggests that doctors test for recurrence at more frequent intervals.